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vitamin d therapy in pediatric patients with inflammatory bowel disease:a systematic review and meta-analysis

World Journal of Pediatrics 2023年第1期19卷 48-57页

作者： Mohammad Hassan Sohouli Fatemeh Farahmand Hosein Alimadadi Parisa Rahmani Farzaneh Motamed Elma Izze da Silva Magalhaes Pejman Rohani Pediatric Gastroenterology and Hepatology Research Center Pediatrics Centre of ExcellenceChildren's Medical CenterTehran University of Medical SciencesTehranIran department of Clinical Nutrition and dietetics Faculty of Nutrition and Food TechnologyShahid Beheshti University of Medical SciencesTehranIran Postgraduate Programme in Collective Health Federal University of MaranhaoRua Barao de Itapary155CentroSao LuísMABrazil Pediatrics Gastroenterology Department of PediatricsSchool of MedicineChildren's Medical CenterTehran University of Medical SciencesTehranIran

Background There is some evidence for the role of vitamin d deficiency in the pathogenesis of inflammatory bowel disease(IBd)in the pediatric ***,the results are ***,we have conducted a systematic review and meta-analysis to evaluated the effect of vitamin d on pediatric patients with *** We carried out a systematic search in databases from inception until 20 January *** included all relevant articles that evaluate the efficacy and safety of vitamin d on disease activity,inflammatory factors,and vitamin d and calcium levels in pediatric patients with *** effects models were used to combine the *** main outcomes were then analyzed using weight mean difference(WMd)and respective 95%confidence interval(CI).Results Fifteen treatment arms met the eligibility criteria and were *** estimates indicated that intervention with vitamin d has a significantly beneficial effect on 25-hydroxy vitamin d3[25(OH)d3](pooled WMd of 17.662 ng/mL;CI 9.77-25.46;Pd WMd of 0.17 mg/dL;CI 0.04-0.30;P=0.009),and inflammatory factors including C-reactive protein(CRP)(pooled WMd of-6.57 mg/L;CI-11.47 to-1.67;P=0.009)and erythrocyte sedimentation rate(ESR)(pooled WMd of-7.94 mm/h;CI-12.65 to-3.22;P=0.001)*** addition,this effect was greater for vitamin d levels at doses greater than 2000 IU,and when follow-up duration was more than 12 *** This study showed that vitamin d therapy can have a significant and beneficial effect on 25(OH)d3,calcium,and inflammatory factors in children and adolescents with IBd.

关键词： disease activity index Inflammation Meta-analysis IBd Pediatric vitamin d

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vitamin d supplementation improves sustained virologic response in chronic hepatitis C (genotype 1)-nave patients

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World Journal of Gastroenterology 2011年第47期17卷 5184-5190页

作者： Saif Abu-Mouch Zvi Fireman Jacob Jarchovsky Abdel-Rauf Zeina Nimer Assy Liver Unit department of Internal Medicine B Hillel Yaffe Medical Center department of Gastroenterology Hillel Yaffe Medical Center Liver Unit Hillel Yaffe Medical Center Liver Unit Ziv Medical Center Technion Institute

AIM: To determine whether adding vitamin d, a potent immunomodulator, improves the hepatitis C virus (HCV) response to antiviral therapy. METHOdS: Seventy-two consecutive patients with chronic HCV genotype 1 were randomized into two groups: the treatment group (n = 36, 50% male, mean age 47 ± 11 years) received Peg-α-2b interferon (1.5 μg/kg per week) plus ribavirin (1000-1200 mg/d) together with vitamin d3 (2000 IU/d, target serum level > 32 ng/mL), and the control group (n = 36, 60% male, mean age 49 ± 7 years) received identical therapy without vitamin d. HCV-RNA was assessed by realtime polymerase chain reaction (sensitivity, 10 IU/mL). The sustained virologic response (SVR) was defined as undetectable HCV-RNA at 24 wk post-treatment. RESULTS: Clinical characteristics were similar in both groups. The treatment group had a higher mean bodymass index (27 ± 4 kg/m2 vs 24 ± 3 kg/m2, P d (50% vs 42%, P d fibrosis score (> F2: 42% vs 19%, P d patients and 6 (17%) controls were HCV-RNA negative (P d patients and 17 (48%) controls were HCV-RNA negative (P d patients and 15 (42%) controls were HCV-RNA negative (P d, advanced fibrosis and vitamin d supplementation were strongly and independently associated with SVR (multivariate analysis). Adverse events were mild and typical of Peg-α-2b/ribavirin. CONCLUSION: Adding vitamin d to conventional Peg-α-2b/ribavirin therapy for treatment-na■ve patients with chronic HCV genotype 1 infection significantly improves the viral response.

关键词： Hepatitis C vitamin d Sustained viral response Genotype 1 Fibrosis

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vitamin d for the prevention and treatment of pancreatic cancer

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World Journal of Gastroenterology 2009年第27期15卷 3349-3354页

作者： Kun-Chun Chiang Tai C Chen department of Surgery Chang Gung Memorial Hospital Chang Gung University Taoyuan 333Taiwan China Boston University School of Medicine 715 Albany Street Boston MA 02118 United States

Pancreatic cancer is ranked fi fth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%. Currently, surgery is the only effective therapy. However, most patients are diagnosed in the late stage and are not suitable for receiving curative surgery. Moreover, pancreatic cancer doesn't respond well to traditional chemotherapy and radiotherapy, leaving little effective treatment for advanced pancreatic cancer cases. 1α,25-dihydroxyvitamin d3 [1α,25(OH)2d3], the biologically active form of vitamin d3, was originally identifi ed during studies of calcium and bone metabolism, though it is now recognized that it exerts biological effects in almost every tissue in the body. Abundant evidence has shown that 1α,25(OH)2d3 has antiproliferative, apoptotic, pro-differentiation and antiangiogensis effects in many types of cancer cells in vivo and in vitro, including breast, prostate, and colon. Similarly, the antitumor growth effect of 1α,25(OH)2d3 on pancreatic cells has been demonstrated. The clinical use of 1α,25(OH)2d3 is impeded by the lethal side effects of hypercalcemia and hypercalciuria. Therefore, 1α,25(OH)2d3 analogs, which are either equipotent or more potent than 1α,25(OH)2d3 in inhibiting tumor cell growth but with fewer hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers. Recently, a pre-clinical study demonstrated that a less calcemic analog of 1α,25(OH)2d3, 19-nor-1α,25(OH)2d2 (Paricalcitol), is effective in inhibiting tumor growth in vitro and in vivo , via upregulation of p21 and p27 tumor suppressor genes. Studies on the anti-tumor effects of a more potent analog of Paricalcitol are underway.1α,25(OH)2d3 and its analogs are potentially attractive novel therapies for pancreatic cancer.

关键词： vitamin d Pancreatic cancer Calcitriol Paricalcitol Chemoprevention Adenocarcinoma CYP27b1

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vitamin d and prevention of breast cancer

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Acta Pharmacologica Sinica 2007年第9期28卷 1373-1382页

作者： JoEllen WELSH department of Biological Sciences University of Notre DameNotre DameIN 46556USA

Epidemiologic data have demonstrated that breast cancer incidence is inverselycorrelated with indices of vitamin d status,including ultraviolet exposure,whichenhances epidermal vitamin d *** vitamin d receptor (VdR) is ex-pressed in mammary epithelial cells,suggesting that vitamin d may directly influ-ence sensitivity of the gland to *** with this concept,invitro studies have demonstrated that the VdR ligand,1,25-dihydroxyvitamin d (1,25d),exerts negative growth regulatory effects on mammary epithelial cells thatcontribute to maintenance of the differentiated ***,deletionof the VdR gene in mice alters the balance between proliferation and apoptosis inthe mammary gland,which ultimately enhances its susceptibility to *** addition,dietary supplementation with vitamin d,or chronic treatment withsynthetic VdR agonists,reduces the incidence of carcinogen-induced mammarytumors in ***,these observations have reinforced the need tofurther define the human requirement for vitamin d and the molecular actions ofthe VdR in relation to prevention of breast cancer.

关键词： vitamin d receptor breast cancer mammary gland vitamin d prevention

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vitamin d deficiency: Correlation to interleukin-17, interleukin-23 and PⅢNP in hepatitis C virus genotype 4

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World Journal of Gastroenterology 2012年第28期18卷 3738-3744页

作者： Mona F Schaalan Waleed A Mohamed Hesham H Amin department of Biochemistry Faculty of Pharmacy Misr International University Cairo 1 Egypt department of Chemistry Cairo University Cairo 11562 Egypt department of Clinical Pathology Faculty of Medicine AL Azhar University Cairo 147 Egypt

AIM: To assess vitamin d (Vit d) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHOdS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit d (i.e., 25-OH-Vit d) and active Vit d [i.e., 1,25-(OH) 2 -Vit d] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit d and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit d and active Vit d was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit d and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P d men and women showed no differences with respect to Vit d levels. The viral load was negatively correlated with Vit d an

关键词： vitamin d Interleukin-17 Interleukin-23 N-terminal propeptide of type Ⅲ pro-collagen Hepatitis genotype 4

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vitamin d improves viral response in hepatitis C genotype 2-3 nave patients

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World Journal of Gastroenterology 2012年第8期18卷 800-805页

作者： Assy Nimer Abu Mouch department of Liver Ziv Medical Center Faculty of Medicine Technion department of Liver Hillel Yaffe Medical Center

AIM: To examine whether vitamin d improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHOdS: Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups: Treatment group [20 subjects, age 48 ± 14 years, body mass index (BMI) 30 ± 6, 65% male], who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV), together with oral vitamin d3 (Vitamidyne d drops; 2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects, age 45 ± 10 years, BMI 26 ± 3, 60% male), who received identical therapy without vitamin d. HCV RNA was assessed by reverse transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (SVR), respectively. Biomarkers of in? ammation were measured. RESULTS: The treatment group with vitamin d hadhigher BMI (30 ± 6 vs 26 ± 3, P d high viral load (> 400 000 IU/mL, 65% vs 40%, P d patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P vitamin d levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin d treatment, to a mean level of (34 ± 11 ng/ mL). Logistic regression analysis identifi ed vitamin d supplement [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P vitamin d levels ( 15 ng/mL, OR 2.2, P d BMI ( 30, OR 2.6, P dependent predictors of viral response. Adverse events were mild and typical of Peg/RBV. CONCLUSION: Low vitamin d levels predicts negative treatment outcome, and adding vitamin d to conventional Peg/RBV therapy for patients with HCV genotype 2-3 signifi cantly improves viral response.

关键词： Hepatitis C Genotype 2-3 vitamin d Sus-tained viral response Peg-interferon alpha 2a

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vitamin d and autoimmune thyroid diseases

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Cellular & Molecular Immunology 2011年第3期8卷 243-247页

作者： Shaye Kivity Nancy Agmon-Levin Michael Zisappl Yinon Shapira Endre V Nagy Katalin danko Zoltan Szekanecz Pnina Langevitz Yehuda Shoenfeld The Zabludovicz Center for Autoimmune diseases Sheba Medical CenterTel-Hashomeraffiliated to Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael department of Medicine‘A&C’ Sheba Medical CenterTel-HashomerIsrael Rheumatic disease Unit Sheba Medical CenterTel-HashomerIsrael department of Medicine‘B’ Sheba Medical CenterTel-HashomerIsrael University of debrecen.Medical and Health Science Center DebrecenHungary Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune diseases Tel Aviv UniversityTel AvivIsrael

The role of vitamin d as an immune modulator has been emphasized in recent years,and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus *** d mediates its effect though binding to vitamin d receptor(VdR),and activation of VdR-responsive *** VdR gene polymorphism was found to associate with autoimmune thyroid diseases(AITds),few studies examined levels of vitamin d in these patients and those that did yielded conflicting *** therefore undertook to evaluate the levels of vitamin d in patients with AITds compared to patients with non-AITds and healthy *** vitamin d(25-OH)levels were measured in 50 patients with AITds,42 patients with non-AITds and 98 healthy subjects,utilizing the LIAISON chemiluminescence immunoassay(diaSorin,Saluggia,Italy).vitamind deficiency was designated at levels lower than 10 ng/*** antibodies,thyroid functions and demographic parameters were evaluated in all *** prevalence of vitamin d deficiency was significantly higher in patients with AITds compared with healthy individuals(72% versus 30.6%;Pditis compared to patients with non-AITds(79% versus 52%;Pvitamin d deficiency also correlated to the presence of antithyroid antibodies(P=0.01)and abnormal thyroid function tests(P=0.059).Significantly low levels of vitamin d were documented in patients with AITds that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests,suggesting the involvement of vitamin d in the pathogenesis of AITds and the advisability of supplementation.

关键词： autoantibodies autoimmune thyroid disease Graves’disease Hashimoto’s thyroiditis vitamin d

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vitamin d improves inflammatory bowel disease outcomes:Basic science and clinical review

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World Journal of Gastroenterology 2014年第17期20卷 4934-4947页

作者： Krista M Reich Richard N Fedorak Karen Madsen Karen I Kroeker division of Gastroenterology University of AlbertaEdmontonAlberta T6G 2X8Canada

vitamin d deficiency is commonly diagnosed among patients with inflammatory bowel disease (IBd). Patients with IBd are at risk of low bone density and increased fractures due to low vitamin d levels, long standing disease, and frequent steroid exposures; as a result, it is well established that vitamin d supplementation in this population is important. There is increasing support for the role of vitamin d in strengthening the innate immune system by acting as an immunomodulator and reducing inflammation in experimental and human IBd. The active form of vitamin d, 1,25(OH)d3, acts on T cells to promote T helper (Th)2/regulatory T responses over Th1/Th17 responses; suppresses dendritic cell inflammatory activity; induces antibacterial activity; and regulates cytokine production in favor of an anti-inflammatory response. Murine and human IBd studies support a therapeutic role of vitamin d in IBd. Risk factors for vitamin d deficiency in this population include decreased sunlight exposure, disease duration, smoking, and genetics. vitamin d normalization is associated with reduced risk of relapse, reduced risk of IBd-related surgeries, and improvement in quality of life. vitamin d is an inexpensive supplement which has been shown to improve IBd outcomes. However, further research is required to determine optimal serum vitamin d levels which will achieve beneficial immune effects, and stronger evidence is needed to support the role of vitamin d in inducing disease response and remission, as well as maintaining this improvement in patients’ disease states.

关键词： vitamin d Inflammatory bowel disease Immune response Inflammation Cytokines Supplementation

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vitamin d deficiency,functional status,and balance in older adults with osteoarthritis

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World Journal of Clinical Cases 2021年第31期9卷 9491-9499页

作者： Cláudia N Montemor Marcos Tadeu P Fernandes Audrey S Marquez Regina Célia Poli-Frederico Rubens Alexandre da Silva Karen B P Fernandes Laboratory of Rehabilitation Research Doctoral Program of Rehabilitation SciencesUniversity Pitágoras Unopar(UNOPAR)Londrina 86041-140ParanaBrazil department of Anesthesiology Irmandade da Santa Casa de LondrinaLondrina 86010-160ParanaBrazil Health Sciences Research Center University Pitágoras Unopar(UNOPAR)Londrina 86041-140ParanaBrazil doctoral Program of Rehabilitation Sciences University Pitagoras Unopar(UNOPAR)Londrina 86041-140ParanaBrazil département des Sciences de la Santé Centre intersectoriel en santédurableLaboratoire de recherche BioNRUniversitédu QuébecàChicoutimi(UQAC)SaguenayG7H 2B1QuébecCanada Centre intégréde santéet services sociaux du Saguenay-Lac-Saint-Jean(CIUSSS SLSJ) Hôpital de La Baie-Services gériatriques spécialisésSaguenayQuébecG7H 7K9Canada

BACKGROUNd Low vitamin d levels are associated with a more severe case of knee osteoarthritis(OA).However,there are few published reports concerning an association between vitamin d deficiency and functional status of individuals with OA and no reports about postural balance in this *** To analyze the relationship between vitamin d deficiency and severity,functional status,and balance in elderly patients with *** In this cross-sectional study,105 elderly patients with hip and knee OA were *** severity was assessed by the Kellgren-Lawrence *** functional status was assessed with the Lequesne *** balance was assessed using a force platform,and center-of-pressure parameters(velocity at anteroposterior and mediolateral axis)were used as the balance *** 25(OH)vitamin d levels were measured using a chemiluminescence *** Most of the patients(mean age:70.6±6.5 years)were female(n=78,74.3%).In the group with vitamin d deficiency,43 patients(56.6%)had severe OA,while 33 patients(43.4%)had mild or moderate OA(χ^(2) test,P=0.04).Patients with vitamin d deficiency showed a higher Lequesne index score(Mann-Whitney test,P=0.04),indicating a worse functional impairment when compared to individuals with normal vitamin d ***,patients with vitamin d deficiency had worse postural balance according to the Mann-Whitney test(P=0.03).CONCLUSION vitamin d deficiency is associated with worse severity,functional status,and postural balance in patients with OA.

关键词： Osteoarthritis Elderly vitamin d disability Severity Balance

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vitamin d attenuates TGF-β1-induced lung fibroblast proliferation and migration through repression of RasGRP3

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BIOCELL 2023年第6期47卷 1243-1251页

作者： GUANQIONG HU RISHENG HUANG LUELUE LU QINSHI PAN XIAOXIN CHEN No.23 Ward of Nursing department The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina department of Thoracic Surgery Wenzhou Central HospitalDingli Clinical College of Wenzhou Medical UniversityWenzhouChina department of Clinical Laboratory The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina

Background:Transforming growth factor-β1(TGF-β1)is a pleiotropic cytokine that plays a central role in the pathogenesis of idiopathic pulmonary fibrosis(IPF).While previous studies have revealed a cross-talk between vitamin d and TGF-β1 signaling,it is still unclear how they interact with each other to regulate the progression of ***:In this work,we searched for a novel mediator of TGF-β1 activity in lung fibroblasts and examined its regulation by vitamin *** addition,we investigated the mechanism underlying the interaction between vitamin d and TGF-β1 signaling in lung fibroblast *** analysis was performed to identify TGF-β1 downstream target *** and overexpression expression experiments were conducted to determine gene function in the regulation of lung fibroblast proliferation and ***:Analysis of publicly available datasets revealed that RAS guanyl releasing protein 3(RasGRP3)was upregulated in TGF-β1-treated lung fibroblasts and lung tissues from IPF patients relative to healthy *** data confirmed the upregulation of RasGRP3 by TGF-β1 in human MRC5 lung *** of RasGRP3 enhanced MRC5 cell proliferation and *** of RasGRP3 blocked TGF-β1-induced MRC5 proliferation and *** d abolished TGF-β1-induced RasGRP3 upregulation,which was reversed by inhibition of the vitamin d receptor(VdR).Mechanistically,vitamin d promoted VdR enrichment and prevented mothers against decapentaplegic homolog(SMAd)2 and 3 occupancy at the promoter of ***,overexpression of RasGRP3 reversed the suppressive effect of vitamin d on MRC5 cell proliferation and ***:In conclusion,vitamin d antagonizes TGF-β1-induced lung fibroblast activation by repressing RasGRP3 transcription.

关键词： Lung fibrosis RasGRP3 TGF-β1 vitamin d

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